Diagnostic Role Of Three-Dimensional System Of Sonographic Image,Cytopathology-histopathology And Molecular Profile For Thyroid Carcinoma

Objective: To investigate the diagnostic roles of thyroid ultrasonography,Fine Needle Aspiration Cytology?FNAC?,Core Needle Biopsy?CNB?and BRAF^V600E Gene mutation testing for Thyroid Carcinoma.Methods:1.A retrospective review of 4606 cases of thyroid nodules in our hospital from January 2015 to December 2016,the ultrasound images were arranged and classified by Thyroid Imaging reporting and data system?TI-RADS?,nodules whose diameter ?1 cm or diameter < 1 cm accompanied by malignant signs of ultrasonography were performed FNAC under ultrasound guidance.The results of Bethesda system for reporting thyroid cytopathology were compared with the final histopathology from surgical resection and clinical follow-ups.The ultrasound images and Bethesda classification were analysed for all nodules,and the proportion of malignant nodules were recorded.The sensitivity,specificity,positive predictive value?PPV?,negative predictive value?NPV?and accuracy of TI-RADS,FNAC-Bethesda classification and combined examination in the diagnosis of thyroid malignant nodules were compared.2.For 170 cases of thyroid nodules whose diagnosis were not confirmed by FNAC using Bethesda system,the ultrasound-guided Core Needle Biopsy was carried out.The histopathologic results from specimens were compared with that of surgical resection.If the nodule diagnosed benign by CNB,the diagnosis were confirmed by repeat FNAC/CNB or follow-up of a stable nodular size not less than 12 months.The sensitivity,specificity,negative predictive value,positive predictive value and accuracy of CNB for the diagnosis of this peculiar thyroid nodules were statistically analyzed.The diagnostic values of CNB and FNAC were compared by areas under receiver operating characteristic curve.3.For the nodules with suspected malignant signs of ultrasound imaging,BRAF^V600Egene mutation were detected from FNAC specimens by amplification refractory mutation system PCR,statistical analysis of BRAF^V600E gene mutations were performed in thyroid nodules of ultrasonographic high-risk,investigate the diagnostic value of BRAF^V600E gene mutation for the ultrasonographic high-risk nodules with Bethesda I^III,according to the histopathological results from surgical resection.Results:1.Reviewing the 4814 thyroid nodules with detailed records,the nodule proportions of TI-RADS 2⁵ were 3.7%?47.7%?47.5% and 1.7%,respectively.Among which,the proportions of nodules with TI-RADS 4a⁴c were 38.7%,7.0%,1.8%,respectively.The proportions of nodules with Bethesda I^VI were 13.3%,59.0%,6.4%,0.7%,15.3% and5.0%,respectively.The sensitivity of TI-RADS and FNAC for the evaluation of benign and malignant thyroid nodules were 79.73% vs 81.72%,the specificity were 66.02% vs99.09%,PPV were 53.50% vs 97.28%,NPV were 86.91% vs 93.16%,the accuracies were70.53% vs 94.14%,respectively.The sensitivity,specificity,PPV,NPV and accuracy of the combination the two methods for evaluation for thyroid nodules were 85.15%,94.77%,82.04%,93.10% and 91.68%,respectively.The areas under the ROC curve of the three evaluation methods were 0.505,0.884 and 0.898,respectively.The diagnostic efficacy of TI-RADS was lower than that of Bethesda classification and combination examination?P <0.01?.2.For the 183 thyroid nodules whose diagnosis were not confirmed by FNAC,nondiagnostic rate was 4.3% when applying CNB.The sensitivity of diagnosis for malignancy by CNB was 80.28%,the specificity was 97.95%,PPV was 96.61%,NPV was86.13% the area under ROC curve was 0.844,it was superior to FNAC whose area under ROC curve was 0.640?P<0.05?.For the nodules with Bethesda I/III results by FNAC,the sensitivity of diagnosis for malignancy by CNB was 83.33%,the specificity was 90.48%,PPV was 90.91%,NPV was 82.61%,the accuracy was 86.67%,the area under ROC curve was 0.869.Two cases were diagnosed diffuse larege B lymphoma by CNB.3.For the 733 high-risk thyroid nodules with one or more than one malignant sign in ultrasound imaging,the proportions of positive rate of BRAF^V600E gene mutation in the nodules with Bethesda I^VI were 35.1%,29.5%,85.4%,0%,87.1% and 92.9%,respectively.For the nodules with Bethesda I and III,the sensitivity of BRAF^V600E gene mutation detection for diagnosis of papillary thyroid carcinoma was 91.30%.Thespecificity was 75.00%,the PPV and NPV were 97.67% and 42.85%,the accuracy was90.00%.The area under ROC curve was 0.832.Forty-four nodules of Bethesda II with BRAF^V600E gene mutation were treated by surgery,forty-two?95.5%?were confirmed papillary thyroid carcinoma by pathology.Conclusions:1.Ultrasonography is an important screening method for thyroid nodules.TI-RADS classification is helpful for stratifying the malignant risk of thyroid nodules,and on this basis,FNAC is performed.The diagnostic accuracies of FNAC and FNAC combined with TIRADS in the diagnosis of benign and malignant thyroid nodules is superior to that of TI-RADS.The two methods can provide accurate information for diagnosis of thyroid nodules,and guide to make clinical management strategies.2.The diagnostic rate of CNB for thyroid nodules which were difficult to diagnose by FNAC is improved,it can provide further diagnostic information for these nodules.CNB is useful supplement to FNAC.3.BRAF^V600E gene mutation is highly effective in the diagnosis of high-risk thyroid nodules in ultrasound imaging,which is important supplement diagnotic tool to FNAC.This mutation is of great significance in preventing the missed diagnosis of papillary thyroid carcinoma in high-risk ultrasonographic nodules with Bethesda I^III readings.